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Mechanisms of neuropathic pain are not fully understood. Molecular changes in spinal dorsal horn take part in the initiation and development of neuropathic pain.
Learn More >Headache is the most common neurologic symptom and affects nearly half the world's population at any given time. Although the prevalence declines with age, headache remains a common neurologic complaint among elderly populations. Headaches can be divided into primary and secondary causes. Primary headaches comprise about two-thirds of headaches among the elderly. They are defined by clinical criteria and are diagnosed based on symptom pattern and exclusion of secondary causes. Primary headaches include migraine, tension-type, trigeminal autonomic cephalalgias, and hypnic headache. Secondary headaches are defined by their suspected etiology. A higher index of suspicion for a secondary headache disorder is warranted in older patients with new-onset headache. They are roughly 12 times more likely to have serious underlying causes and, frequently, have different symptomatic presentations compared to younger adults. Various imaging and laboratory evaluations are indicated in the presence of any "red flag" signs or symptoms. Head CT is the procedure of choice for acute headache presentations, and brain MRI for those with chronic headache complaints. Management of headache in elderly populations can be challenging due to the presence of multiple medical comorbidities, polypharmacy, and differences in drug metabolism and clearance.
Learn More >Nonsteroidal anti-inflammatory drugs and acetaminophen are cyclooxygenase inhibitors commonly used as symptomatic medicines for myofascial pain syndrome. Using the selective inhibitors celecoxib and zaltoprofen, cyclooxygenase-2 has been shown to be involved in the initiation, but not the maintenance, of muscular mechanical hyperalgesia induced by lengthening contractions, which serves as a useful model for the study of myofascial pain syndrome. The effect of other cyclooxygenase-2 inhibitors, such as acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen, on muscular mechanical hyperalgesia during maintenance has not been studied. Here, we examined the analgesic effects of the nonsteroidal anti-inflammatory drugs and acetaminophen on the model. Consistent with previous studies, mechanical withdrawal threshold of the muscle was significantly decreased and reached its lowest level 24 h after lengthening contractions. Celecoxib had no effect on muscular mechanical hyperalgesia, when orally administered 24 h after lengthening contractions. In contrast, acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen increased the withdrawal threshold, which had decreased by lengthening contractions, in a dose-dependent manner. These results demonstrate the analgesic actions of nonsteroidal anti-inflammatory drugs and acetaminophen in the maintenance process of lengthening contraction-induced muscular mechanical hyperalgesia, which may occur through cyclooxygenase-2 independent mechanisms.
Learn More >Chronic pain is a major health problem, affecting 10-30% of the population in developed countries. While chronic pain is defined as "a persistent complaint of pain lasting for more than the usual period for recovery," recently accumulated lines of evidence based on human brain imaging have revealed that chronic pain is not simply a sustained state of nociception, but rather an allostatic state established through gradually progressing plastic changes in the central nervous system. To visualize the brain activity associated with spontaneously occurring pain during the shift from acute to chronic pain under anesthetic-free conditions, we used manganese-enhanced magnetic resonance imaging (MEMRI) with a 9.4-T scanner to visualize neural activity-dependent accumulation of manganese in the brains of mice with hind paw inflammation. Time-differential analysis between 2- and 6-h after formalin injection to the left hind paw revealed a significantly increased MEMRI signal in various brain areas, including the right insular cortex, right nucleus accumbens, right globus pallidus, bilateral caudate putamen, right primary/secondary somatosensory cortex, bilateral thalamus, right amygdala, bilateral substantial nigra, and left ventral tegmental area. To analyze the role of the right amygdala in these post-formalin MEMRI signals, we repeatedly inhibited right amygdala neurons during this 2-6-h period using the "designer receptors exclusively activated by designer drugs" (DREADD) technique. Pharmacological activation of inhibitory DREADDs expressed in the right amygdala significantly attenuated MEMRI signals in the bilateral infralimbic cortex, bilateral nucleus accumbens, bilateral caudate putamen, right globus pallidus, bilateral ventral tegmental area, and bilateral substantia nigra, suggesting that the inflammatory pain-associated activation of these structures depends on the activity of the right amygdala and DREADD-expressing adjacent structures. In summary, the combined use of DREADD and MEMRI is a promising approach for revealing regions associated with spontaneous pain-associated brain activities and their causal relationships.
Learn More >Growing evidence indicates cannabinoid receptors as potential therapeutic targets for chronic pain. Consequently, there is an increasing interest in developing cannabinoid receptor agonists for treating human and veterinary pain. To better understand the actions of a drug, it is of paramount importance to know the cellular distribution of its specific receptor(s). The distribution of canonical and putative cannabinoid receptors in the peripheral and central nervous system of dogs is still in its infancy. In order to help fill this anatomical gap, the present study has been designed to identify the cellular sites of cannabinoid and cannabinoid-related receptors in canine spinal ganglia. In particular, the cellular distribution of the cannabinoid receptors type 1 and 2 (CB and CB) and putative cannabinoid receptors G protein-coupled receptor 55 (GPR55), nuclear peroxisome proliferator-activated receptor alpha (PPARα), and transient receptor potential vanilloid type 1 (TRPV1) have been immunohistochemically investigated in the C6-C8 cervical ganglia of dogs. About 50% of the neuronal population displayed weak to moderate CB receptor and TRPV1 immunoreactivity, while all of them were CB-positive and nearly 40% also expressed GPR55 immunolabeling. Schwann cells, blood vessel smooth muscle cells, and pericyte-like cells all expressed CB receptor immunoreactivity, endothelial cell being also PPARα-positive. All the satellite glial cells (SGCs) displayed bright GPR55 receptor immunoreactivity. In half of the study dogs, SGCs were also PPARα-positive, and limited to older dogs displayed TRPV1 immunoreactivity. The present study may represent a morphological substrate to consider in order to develop therapeutic strategies against chronic pain.
Learn More >Recent findings from rodent studies suggest that high-fat diet (HFD) increases hyperalgesia independent of obesity status. Furthermore, weight loss interventions such as voluntary physical activity (PA) for adults with obesity or overweight was reported to promote pain reduction in humans with chronic pain. However, regardless of obesity status, it is not known whether HFD intake and sedentary (SED) behavior is underlies chronic pain susceptibility. Moreover, differential gene expression in the nucleus accumbens (NAc) plays a crucial role in chronic pain susceptibility. Thus, the present study used an adapted model of the inflammatory prostaglandin E2 (PGE2)-induced persistent hyperalgesia short-term (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. Therefore, we performed an analysis of differential gene expression using a transcriptome approach of the NAc. We also applied a gene ontology enrichment tools to identify biological processes associated with chronic pain susceptibility and to investigate the interaction between the factors studied: diet (standard diet vs. HFD), physical activity behavior (SED vs. PA) and PH-ST (PGE vs. saline). Our results demonstrated that HFD intake and sedentary behavior promoted chronic pain susceptibility, which in turn was prevented by voluntary physical activity, even when the animals were fed an HFD. The transcriptome of the NAc found 2,204 differential expression genes and gene ontology enrichment analysis revealed 41 biologic processes implicated in chronic pain susceptibility. Taking these biological processes together, our results suggest that genes related to metabolic and mitochondria stress were up-regulated in the chronic pain susceptibility group (SED-HFD-PGE), whereas genes related to neuroplasticity were up-regulated in the non-chronic pain susceptibility group (PA-HFD-PGE). These findings provide pieces of evidence that HFD intake and sedentary behavior provoked gene expression changes in the NAc related to promotion of chronic pain susceptibility, whereas voluntary physical activity provoked gene expression changes in the NAc related to prevention of chronic pain susceptibility. Finally, our findings confirmed previous literature supporting the crucial role of voluntary physical activity to prevent chronic pain and suggest that low levels of voluntary physical activity would be helpful and highly recommended as a complementary treatment for those with chronic pain.
Learn More >Chronic pelvic pain syndrome (CPPS) is a multifactorial disorder comprising structural and functional muscular abnormalities, a dysfunctional pain system, and psychological distress. Myofascial physical Therapy (MPT) that is targeted at improving pelvic muscle functioning is considered a first line nonpharmacological treatment for CPPS, although the precise mechanisms that lead to symptoms alleviation have not yet been elucidated.
Learn More >Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients.
Learn More >Assessing features of centralized pain may prove to be clinically meaningful in pediatric populations. However, we are currently limited by the lack of validated pediatric measures.
Learn More >Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is one of the essential signaling pathways for the development and maintenance of neuropathic pain.
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